Abstract 393: Differential Regulation of Lipoprotein Assembly and Secretion and Mtp Expression in Intestinal and Hepatic Cells by Oleoylethanolamide

Dietary fat triggers synthesis of OEA in enterocytes of the upper small intestine. OEA initiates a cascade of events to optimize fatty acid uptake and reduce feeding frequency. Effects of OEA have been studied after oral gavage and intraperitoneal injections. Here, we studied dose dependent effects of OEA on the assembly and secretion of lipoproteins in differentiated human colon carcinoma Caco-2, human hepatoma Huh-7 and HepG2 cells as well as in mouse primary enterocytes and hepatocytes. Differentiated Caco-2 cells were treated with OEA or oleic acid for 16 h. OEA increased synthesis of triglycerides in dose dependent manner compared with oleic acid:taurocholate micelles. Further, OEA increased secretion of triglycerides and apolipoprotein B (apoB) in chylomicrons. Expression and activity of microsomal triglyceride transfer protein (MTP) was increased by OEA in a dose dependent manner in these cells. Next, mouse primary enterocytes were incubated with OEA or oleic acid for 4 h. OEA increased MTP activity and secretion of triglycerides in these cells as well. These studies suggest that OEA enhances MTP expression, lipid synthesis and lipoprotein assembly in intestinal cells more than oleic acid. To study the effect of OEA on liver derived cells, these cells were exposed to OEA or no lipids for 16 h. OEA reduced secretion of triglycerides and apoB in Huh-7 and HepG2 cells without affecting the secretion of apoAI. Further, MTP expression and activity was reduced in these cells after OEA treatment compared to no OEA controls. Similarly, OEA reduced MTP expression and activity as well as secretion of triglycerides in mouse primary hepatocytes. These studies indicate that OEA reduces MTP expression, lipid synthesis and lipoproteins secretion in liver derived cells. Thus, OEA has differential effects on MTP expression and lipoprotein assembly and secretion in intestine and liver derived cells. It is likely that OEA regulates postprandial response to optimize exogenous lipid absorption and reduce endogenous lipid mobilization.